Vishweswaraiah Sangeetha, Ramachandra Nallur B, Joshi Neha, Parthasarathi Ashwaghosha, Kaleem Ullah Mohammed, Siddaiah Jayaraj Biligere, Holla Amrutha D, Chakraborty Samarpana, Agrawal Anurag, Mahesh Padukudru Anand
Department of Studies in Genetics and Genomics, University of Mysore, Manasagangotri, Mysore 570006, India.
Department of Respiratory Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India.
Diagnostics (Basel). 2023 Jan 22;13(3):405. doi: 10.3390/diagnostics13030405.
has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case-control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of , namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele "T" for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population.
已与哮喘患者的气道结构变化相关联，导致气道高反应性、狭窄，并最终导致治疗反应不佳。本研究旨在评估单核苷酸多态性（SNPs）与南印度人群哮喘、疾病严重程度以及对吸入性糖皮质激素+长效β2受体激动剂（ICS+LABA）治疗反应性之间的遗传关联。在这项病例对照研究（486名对照者和503名病例）中，我们使用MassArray对六个SNPs进行基因分型，即rs2280091、rs2787094、rs3918396、rs67044、rs2853209和rs3918392。我们通过基因型、等位基因频率分布和单倍型分析研究了与哮喘以及对ICS+LABA治疗反应性的关联。该研究的一个重要临床发现是，疾病严重程度组（中度和轻度）中的某些患者在接受为期三个月的规律ICS+LABA治疗随访后，病情改善不佳或无改善。在所研究的SNPs中，rs2853209与哮喘相关联。根据疾病严重程度对哮喘患者进行的进一步分析表明，中度疾病与rs2853209的次要等位基因“T”之间存在关联。发现SNPs rs2787094的纯合次要等位基因与较差的肺功能以及在接受三个月ICS+LABA治疗后肺功能改善最少相关。对六个SNPs的单倍型分析表明，rs2853209和rs3918396区域与哮喘之间存在显著关联。基因多态性在疾病关联和治疗反应方面具有临床相关性。SNPs rs2853209似乎与哮喘最为相关，而SNPs rs2787094可能是预测研究人群对ICS+LABA治疗反应的遗传标志物。
